The present invention relates to a process for producing staurosporine derivatives. The present invention further relates to a novel staurosporine derivative.
Staurosporine is a known anti-tumor agent having the following formula: ##STR2##
As the staurosporine derivatives, UCN-01 having anti-tumor activity is known (EP-A-238011, U.S. Pat. No. 4,935,415). Further, stereoisomers of UCN-01 are disclosed in Journal of Antibiotics, 42, 564 (1989); and derivatives of UCN-01, are disclosed in WO89/07105.
The following two methods have heretofore been known, for producing UCN-01:
(1) A fermentation method which comprises culturing a microorganism belonging to the genus Streptomyces and having an ability to produce UCN-01 in a medium, and recovering UCN-01 therefrom (U.S. Pat. No. 4,935,415). PA1 (2) A chemically synthetic method which comprises oxidizing Compound (A) represented by the formula (A), which is easily produced from staurosporine with lead tetraacetate in acetic acid and removing the protecting group by the catalytic reduction of the oxidized product of Compound (A) to afford UCN-01 (European Publication No. 383,919). ##STR3## PA1 Y represents a single bond or --CH(OH)-- PA1 Z represents hydroxy, OCON R.sup.1 R.sup.2, in which each of R.sup.1 and R.sup.2 independently represents hydrogen or lower alkyl, or R.sup.1 and R.sup.2, combined together with the nitrogen atom adjacent thereto, form a heterocyclic group carboxyl, PA1 N R.sup.3 R.sup.4, in which each of R.sup.3 and R.sup.4 independently represents hydrogen or lower alkyl, or R.sup.3 and R.sup.4, combined together with the nitrogen atom adjacent thereto, form a heterocyclic group or, substituted or unsubstituted aryl, PA1 each of m and n independently represents an integer of from 0 to 6, PA1 Y represents a single bond or --CH(OH)-- PA1 Z represents hydroxy, O C O N R.sup.1 R.sup.2, in which each of R.sup.1 and R.sup.2 independently represents hydrogen or lower alkyl, or R.sup.1 and R.sup.2, combined together with the nitrogen atom adjacent thereto, form a heterocyclic group carboxyl, N R.sup.3 R.sup.4, in which each of R.sup.3 and R.sup.4 independently represents hydrogen or lower alkyl, or R.sup.3 and R.sup.4, combined together with the nitrogen atom adjacent thereto, form a heterocyclic group or, substituted or unsubstituted aryl, PA1 each of m and n independently represents an integer of from 0 to 6,
However, the potency in the fermentation method is low; and the yield in the chemically synthetic method is low since the method involves three steps for obtaining UCN-01.